Cardiomyocyte mechanodynamics under conditions of actin remodelling

Ricardo H. Pires, Nithya Shree, Emmanuel Manu, Ewa Guzniczak, Oliver Otto

Research output: Contribution to journalArticle

2 Citations (Scopus)
3 Downloads (Pure)

Abstract

The mechanical performance of cardiomyocytes (CMs) is an important indicator of their maturation state and of primary importance for the development of therapies based on cardiac stem cells. As the mechanical analysis of adherent cells at high-throughput remains challenging, we explore the applicability of real-time deformability cytometry (RT-DC) to probe cardiomyocytes in suspension. RT-DC is a microfluidic technology allowing for real-time mechanical analysis of thousands of cells with a throughput exceeding 1000 cells per second. For CMs derived from human-induced pluripotent stem cells, we determined a Young's modulus of 1.25 ± 0.08 kPa which is in close range to previous reports. Upon challenging the cytoskeleton with cytochalasin D (CytoD) to induce filamentous actin depolymerization, we distinguish three different regimes in cellular elasticity. Transitions are observed below 10 nM and above 103 nM and are characterized by a decrease in Young's modulus. These regimes can be linked to cytoskeletal and sarcomeric actin contributions by CM contractility measurements at varying CytoD concentrations, where we observe a significant reduction in pulse duration only above 103 nM while no change is found for compound exposure at lower concentrations. Comparing our results to mechanical cellmeasurements using atomic force microscopy, we demonstrate for the first time to our knowledge, the feasibility of using a microfluidic technique to measure mechanical properties of large samples of adherent cells while linking our results to the composition of the cytoskeletal network.

Original languageEnglish
Article number20190081
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume374
Issue number1786
Early online date7 Oct 2019
DOIs
Publication statusPublished - Nov 2019

Keywords

  • cardiomyocytes
  • cell mechanics
  • contractility
  • real-time deformability cytometry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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